AVM0703 combined with Non-Hodgkin's Lymphoma standard of care to enhance complete response rates without additional toxicities

AVM0703 与非霍奇金淋巴瘤护理标准相结合，可提高完全缓解率，且不会产生额外毒性

• 批准号: 10546563
• 负责人: Theresa Deisher
• 金额: $ 39.92万
• 依托单位: AVM BIOTECHNOLOGY, LLC
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-05 至 2023-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10546563
• 关键词: Acute; Adverse effects; Agammaglobulinaemia tyrosine kinase; Age; B-Cell NonHodgkins Lymphoma; Biotechnology; Blood; Body Weight decreased; Bone Marrow; Burkitt Lymphoma; Cancer Etiology; Cancerous; Cardiotoxicity; Cell Line; Cells; Chemotherapy-Oncologic Procedure; Clinical; Clinical Research; Clinical Trials; Combined Modality Therapy; Cyclophosphamide; DNA; Data; Death Rate; Desire for food; Dexamethasone; Diagnosis; Disease remission; Dose; Doxorubicin; Economic Burden; Elderly; Endotoxins; Evolution; Excipients; Exposure to; Feeling; Formulation; Frequencies; Genomics; Glucocorticoids; Goals; Growth; Health; Healthcare; Hour; In complete remission; Inbred BALB C Mice; Infusion procedures; Intravenous; Invaded; Lymphocyte; Lymphoma; Lymphoma cell; Malignant Neoplasms; Measurement; Modeling; Monoclonal Antibody CD20; Mus; Newly Diagnosed; Non-Hodgkin' s Lymphoma; Outcome; Package Insert; Patients; Pharmaceutical Preparations; Phase; Placebos; Population; Prednisone; Quality of life; Recurrence; Refractory; Regimen; Relapse; Reporting; Risk; Rogaine; Safety; Second Primary Cancers; Small Business Innovation Research Grant; Spleen; Therapeutic; Time; Toxic effect; Toxicology; Tumor Volume; Tyrosine Kinase Inhibitor; Vincristine; anti-CD20; base; cancer diagnosis; cancer therapy; chemotherapy; combinatorial; cost; efficacy study; experience; immune resistance; improved; inhibitor; innovation; large cell Diffuse non-Hodgkin' s lymphoma; mouse model; neurotoxicity; non-Hodgkin' s lymphoma patients; novel; novel strategies; novel therapeutics; older patient; patient population; patient subsets; pre-clinical; response; rituximab; side effect; sodium phosphate; standard of care; tositumomab; treatment strategy; tumor

PROJECT SUMMARY Non-Hodgkin’s Lymphoma (NHL) represents 4% of all cancer diagnosed in the U.S., and as many as 50% of patients will relapse within 2 years of diagnosis and treatment. The current standard of care is chemotherapy. For Diffuse Large B cell Lymphoma subtype (DLBCL) CHOP (cyclophosphamide- doxorubicin-vincristine-prednisone) is given in combination with an anti-CD20 monoclonal antibody, such as rituximab (R-CHOP). Unfortunately, chemotherapy requires numerous treatment cycles with challenging side effects and does not completely remove the cancerous lymphocytes, as indicated by the frequency of relapse. A drug that could reduce the lymphoma population and essentially increase the potency of the chemotherapy regimen (fewer lymphoma cells to the chemotherapy concentration) would have the potential to be synergistic as a treatment strategy. AVM0703, a proprietary formulation of high concentration dexamethasone developed by AVM Biotechnology, has been shown to control NHL growth in murine models. It also safely reduces lymphocytes following a single very high dose via one-hour infusion, in both pre-clinical and clinical settings. AVM0703 is currently the subject of a US-based clinical study in no-option, relapsed/refractory NHL patients and is distinguished from other investigative drugs in this ‘terminal no-option’ patient population by its absence of safety concerns with patients reporting feeling great, regaining appetite and energy, and durable response recorded. The goal of this project is to validate the combination of AVM0703 and standard DLBCL chemotherapy R-CHOP. This approach is expected to increase complete response rates and potentially reduce the required number of chemotherapy cycles, providing a more tolerable therapeutic option for newly diagnosed NHL patients. The feasibility of this approach will be validated in Phase I with the following aims: Aim 1) Evaluate the ability of AVM0703 in combination with R-CHOP to reduce R-CHOP cycles in an aggressive, immune-resistant murine B cell NHL model. Aim 2) Assessment of AVM0703 combination therapy with reduced dose R-CHOP to enhance outcomes in elderly patients. The Phase II project will further focus on efficacy studies, and a small clinical trial with newly diagnosed NHL patients to evaluate the effects of this novel therapeutic treatment approach.

项目摘要 非霍奇金淋巴瘤（NHL）占美国诊断的所有癌症的4%，多达50% 的患者在诊断和治疗后2年内会复发。目前的护理标准是 化疗对于弥漫性大B细胞淋巴瘤亚型（DLBCL），CHOP（环磷酰胺- 多柔比星-长春新碱-泼尼松）与抗CD 20单克隆抗体，如 利妥昔单抗（R-CHOP）。不幸的是，化疗需要大量的治疗周期， 如复发频率所示，其影响并且不完全去除癌性淋巴细胞。 一种可以减少淋巴瘤人口并从根本上提高化疗效力的药物 化疗方案（相对于化疗浓度，淋巴瘤细胞较少）将具有协同作用的潜力 作为治疗策略。AVM 0703，高浓度地塞米松的专有配方 由AVM Biotechnology开发的，已显示在鼠模型中控制NHL生长。它也安全地 在临床前和临床中，通过1小时输注单次极高剂量后减少淋巴细胞 设置. AVM 0703目前是一项基于美国的无选择、复发性/难治性NHL临床研究的主题 患者，与该“终末期无选择”患者人群中的其他研究药物的区别在于： 患者报告感觉良好，恢复食欲和精力， 记录的持久响应。本项目的目标是验证AVM 0703和标准的组合 DLBCL化疗R-CHOP。预计这一办法将提高完全反应率， 可能减少所需的化疗周期数，提供更耐受的治疗选择 新诊断的NHL患者。这一方法的可行性将在第一阶段得到验证， 以下目的：目的1）评价AVM 0703与R-CHOP联合使用降低R-CHOP的能力 在侵袭性、免疫抗性鼠B细胞NHL模型中的周期。目的2）AVM 0703的评估 与减少剂量的R-CHOP联合治疗，以提高老年患者的结局。II期 该项目将进一步关注疗效研究，并对新诊断的NHL患者进行小型临床试验， 评估这种新的治疗方法的效果。